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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2006-05-22 14:17:39 UTC
Update Date2022-03-07 02:49:13 UTC
HMDB IDHMDB0002174
Secondary Accession Numbers
  • HMDB02174
Metabolite Identification
Common NameCobalamin
DescriptionCobalamin participates in two enzymatic processes in mammalian cells. In the methionine synthase (EC 2.1.1.13) reaction, homocysteine (HCys) is converted to methionine allowing for the "recycling" of 5-methyl-tetrahydrofolate (THF) to N5,10 methylene-THF which is needed for the de novo synthesis of thymidylic acid and ultimately, for DNA formation. Since conversion of N5,10-methylene-THF to N5-methyl-THF is irreversible, cobalamin deficiency "traps" folic acid as N5-methyl-THF. Concurrently, HCys accumulates while methionine decreases, leading to a decrease in S-adenosylmethionine which further limits N5,10-methylene-THF formation by decreasing the synthesis of formyl-THF ("formate starvation"). Decreased methionine and S-adenosylmethionine may limit many methylation reactions including those involving DNA and myelin basic protein. In the methylmalonyl CoA mutase (EC 5.1.99.1) reaction, methylmalonyl CoA, derived from propionic acid synthesized by intestinal bacteria, is converted to succinyl CoA, a precursor for fatty acid and heme synthesis Thus, cobalamin deficiency results in methylmalonic acid (MMA) accumulation. Cobalamin deficiency causes megaloblastic anemia and neurocognitive abnormalities but effects on immune function and bone formation have also been described. Low serum cobalamin levels increase the risk of osteoporosis. Tests for cobalamin deficiency include measurements of 1) total cobalamin; 2) MMA and HCys, as indices of functional cobalamin deficiency; and 3) holotranscobalamin as a measure of the metabolically active fraction of circulating cobalamin. Each approach has significant limitations. Moreover, since the pathogenesis of neurologic dysfunction in cobalamin deficiency remains unclear, these tests may not be reliable markers of neurocognitive impairment. Subtle cobalamin deficiency, defined as elevated metabolite levels usually in asymptomatic patients with low or normal serum cobalamin values, is prevalent in the elderly and has been associated with food cobalamin malabsorption, a disorder characterized by the inability to release vitamin B12 from food or from its binding proteins. Malabsorption is often unrecognized or not investigated. However, because of the potential seriousness of the complications, particularly neuropsychiatric and hematological investigation of all patients who present with vitamin or nutritional deficiency is required. Classic disorders, such as pernicious anemia, are the cause of cobalamin deficiency in only a limited proportion of elderly patients. Epidemiological studies have shown a prevalence of cobalamin deficiency of around 20% in the elderly population of industrialized countries (between 50% and 60%, depending on the definition of cobalamin deficiency used in the study). New routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption. (PMID: 16814909 , 17822656 ).
Structure
Thumb
Synonyms
Chemical FormulaC62H88CoN13O14P
Average Molecular Weight1329.369
Monoisotopic Molecular Weight1328.563777
IUPAC Name(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-46-hydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2lambda5,9,19,26,43lambda5,44lambda5,45lambda5-heptaaza-15lambda5-phospha-1-cobaltadodecacyclo[27.14.1.1^{1,34}.1^{2,9}.1^{10,13}.0^{1,26}.0^{3,8}.0^{23,27}.0^{25,42}.0^{32,44}.0^{39,43}.0^{37,45}]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1-diuid-15-olate
Traditional Name(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-46-hydroxy-12-(hydroxymethyl)-5,6,17,23,28,31,31,36,38,41,42-undecamethyl-15,20-dioxo-11,14,16-trioxa-2lambda5,9,19,26,43lambda5,44lambda5,45lambda5-heptaaza-15lambda5-phospha-1-cobaltadodecacyclo[27.14.1.1^{1,34}.1^{2,9}.1^{10,13}.0^{1,26}.0^{3,8}.0^{23,27}.0^{25,42}.0^{32,44}.0^{39,43}.0^{37,45}]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1-diuid-15-olate
CAS Registry Number13408-78-1
SMILES
[H][C@]12[C@H](CC(N)=O)[C@@]3(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]4[C@@H](O)[C@H](O[C@@H]4CO)N4C=[N+](C5=CC(C)=C(C)C=C45)[Co--]456N1C3=C(C)C1=[N+]4C(=CC3=[N+]5C(=C(C)C4=[N+]6[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]4CCC(N)=O)[C@@](C)(CC(N)=O)[C@@H]3CCC(N)=O)C(C)(C)[C@@H]1CCC(N)=O
InChI Identifier
InChI=1S/C62H90N13O14P.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);/q;+3/p-2/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;/m1./s1
InChI KeyNSLAUEAQDBERRV-DSRCUDDDSA-L
Chemical Taxonomy
Description Belongs to the class of organic compounds known as cobalamin derivatives. These are organic compounds containing a corrin ring, a cobalt atom, an a nucleotide moiety. Cobalamin Derivatives are actually derived from vitamin B12.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTetrapyrroles and derivatives
Sub ClassCorrinoids
Direct ParentCobalamin derivatives
Alternative Parents
Substituents
  • Cobalamin
  • Metallotetrapyrrole skeleton
  • 1-ribofuranosylbenzimidazole
  • Pentose phosphate
  • N-glycosyl compound
  • Glycosyl compound
  • Monosaccharide phosphate
  • Pentose monosaccharide
  • Benzimidazole
  • Phosphoethanolamine
  • Dialkyl phosphate
  • Monosaccharide
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Phosphoric acid ester
  • Alkyl phosphate
  • Benzenoid
  • Fatty amide
  • Fatty acyl
  • Pyrroline
  • Pyrrolidine
  • Imidazole
  • Azole
  • Tetrahydrofuran
  • Heteroaromatic compound
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Carboxamide group
  • Ketimine
  • Oxacycle
  • Azacycle
  • Organic transition metal salt
  • Carbene-type 1,3-dipolar compound
  • Carboxylic acid derivative
  • Alcohol
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Imine
  • Primary alcohol
  • Organic salt
  • Organic cobalt salt
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organic cation
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
Biological locationSource
Process
Role
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
Predicted Chromatographic Properties

Predicted Kovats Retention Indices

Not Available
Spectra
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue Locations
  • Erythrocyte
  • Fibroblasts
  • Intestine
  • Liver
  • Neuron
  • Placenta
Pathways
Normal Concentrations
Abnormal Concentrations
Associated Disorders and Diseases
Disease References
Pregnancy
  1. Shiraishi M, Haruna M, Matsuzaki M, Murayama R, Sasaki S, Murashima S: Validity and reproducibility of folate and vitamin B(12) intakes estimated from a self-administered diet history questionnaire in Japanese pregnant women. Nutr J. 2012 Mar 15;11:15. doi: 10.1186/1475-2891-11-15. [PubMed:22420377 ]
Transcobalamin II deficiency
  1. Bibi H, Gelman-Kohan Z, Baumgartner ER, Rosenblatt DS: Transcobalamin II deficiency with methylmalonic aciduria in three sisters. J Inherit Metab Dis. 1999 Oct;22(7):765-72. [PubMed:10518276 ]
Cobalamin F disease (cblF)
  1. Alfadhel M, Lillquist YP, Davis C, Junker AK, Stockler-Ipsiroglu S: Eighteen-year follow-up of a patient with cobalamin F disease (cblF): report and review. Am J Med Genet A. 2011 Oct;155A(10):2571-7. doi: 10.1002/ajmg.a.34220. Epub 2011 Sep 9. [PubMed:21910240 ]
Megaloblastic anemia 1
  1. WATERS AH, MURPHY ME: Familial juvenile pernicious anaemia: a study of the hereditary basis of pernicious anaemia. Br J Haematol. 1963 Jan;9:1-12. [PubMed:13999146 ]
Multiple sclerosis
  1. Scalabrino G, Galimberti D, Mutti E, Scalabrini D, Veber D, De Riz M, Bamonti F, Capello E, Mancardi GL, Scarpini E: Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis. Brain Res. 2010 May 28;1333:64-71. doi: 10.1016/j.brainres.2010.03.073. Epub 2010 Mar 27. [PubMed:20347721 ]
Cystic fibrosis
  1. Scalabrino G, Galimberti D, Mutti E, Scalabrini D, Veber D, De Riz M, Bamonti F, Capello E, Mancardi GL, Scarpini E: Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis. Brain Res. 2010 May 28;1333:64-71. doi: 10.1016/j.brainres.2010.03.073. Epub 2010 Mar 27. [PubMed:20347721 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022886
KNApSAcK IDC00001534
Chemspider ID5256728
KEGG Compound IDC05776
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCobalamin
METLIN ID6527
PubChem Compound6857388
PDB IDNot Available
ChEBI ID28911
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDMDB00000382
Good Scents IDNot Available
References
Synthesis ReferenceAbou-Zeid, A. A.; El-Sherbeeny, M. R. Production of cobalamin by Streptomyces olivaceus. Indian Journal of Technology (1976), 14(7), 357-9.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, de la Chapelle A, He Q, Moestrup SK: The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood. 2004 Mar 1;103(5):1573-9. Epub 2003 Oct 23. [PubMed:14576052 ]
  2. Urban G, Pietrzik K, Hotzel D: [Radiological investigations of cobalamin supply with regard to folate status (author's transl)]. Int J Vitam Nutr Res. 1981;51(2):124-31. [PubMed:7287335 ]
  3. Kanazawa S, Herbert V: Total corrinoid, cobalamin (vitamin B12), and cobalamin analogue levels may be normal in serum despite cobalamin in liver depletion in patients with alcoholism. Lab Invest. 1985 Jul;53(1):108-10. [PubMed:4010227 ]
  4. Minato H, Inada A, Kozaka S: [The effect of the external biliary diversion on cobalamin functions]. Nihon Geka Gakkai Zasshi. 1995 Oct;96(10):695-702. [PubMed:8538588 ]
  5. Hansen PK, Byskov J, Gimsing P, Hippe E, Ladefoged K: Cobalamin absorption determined by the stool spot test. Reliability in patients with uremia or disorders of the ileum. Scand J Gastroenterol. 1986 Apr;21(3):341-7. [PubMed:3086965 ]
  6. Ermens AA, Vlasveld LT, van Marion-Kievit JA, Lensen CJ, Lindemans J: [The significance of an elevated cobalamin concentration in the blood]. Ned Tijdschr Geneeskd. 2002 Mar 9;146(10):459-64. [PubMed:11913109 ]
  7. Lott WB, Takyar SS, Tuppen J, Crawford DH, Harrison M, Sloots TP, Gowans EJ: Vitamin B12 and hepatitis C: molecular biology and human pathology. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4916-21. Epub 2001 Apr 10. [PubMed:11296247 ]
  8. Haltmayer M, Mueller T, Poelz W: Erythrocyte mean cellular volume and its relation to serum homocysteine, vitamin B12 and folate. Acta Med Austriaca. 2002;29(2):57-60. [PubMed:12050947 ]
  9. Baker H, Leevy CB, DeAngelis B, Frank O, Baker ER: Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease. J Am Coll Nutr. 1998 Jun;17(3):235-8. [PubMed:9627908 ]
  10. Watkins D, Matiaszuk N, Rosenblatt DS: Complementation studies in the cblA class of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH). J Med Genet. 2000 Jul;37(7):510-3. [PubMed:10882753 ]
  11. Ermens AA, Vlasveld LT, Lindemans J: Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003 Nov;36(8):585-90. [PubMed:14636871 ]
  12. Solomon LR: Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev. 2007 May;21(3):113-30. Epub 2006 Jul 11. [PubMed:16814909 ]
  13. Andres E, Vidal-Alaball J, Federici L, Loukili NH, Zimmer J, Kaltenbach G: Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy. Eur J Intern Med. 2007 Oct;18(6):456-62. Epub 2007 Jul 12. [PubMed:17822656 ]

Enzymes

General function:
Involved in cobalamin binding
Specific function:
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).
Gene Name:
MTR
Uniprot ID:
Q99707
Molecular weight:
140525.91
General function:
Involved in isomerase activity
Specific function:
Involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle. MCM has different functions in other species.
Gene Name:
MUT
Uniprot ID:
P22033
Molecular weight:
83133.755
General function:
Involved in nucleotide binding
Specific function:
Probable GTPase. May function as chaperone. May be involved in the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis
Gene Name:
MMAA
Uniprot ID:
Q8IVH4
Molecular weight:
46537.9
General function:
Involved in cobalamin binding
Specific function:
May be involved in the binding and intracellular trafficking of cobalamin (vitamin B12)
Gene Name:
MMACHC
Uniprot ID:
Q9Y4U1
Molecular weight:
31728.1
General function:
Involved in growth factor activity
Specific function:
Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10. Receptor for the cellular uptake of transcobalamin bound cobalamin
Gene Name:
CD320
Uniprot ID:
Q9NPF0
Molecular weight:
28990.6
General function:
Involved in cobalamin binding
Specific function:
Not Available
Gene Name:
TCN2
Uniprot ID:
B5MBX2
Molecular weight:
47142.1

Transporters

General function:
Involved in cobalamin binding
Specific function:
Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells
Gene Name:
TCN2
Uniprot ID:
P20062
Molecular weight:
47534.5
General function:
Involved in cobalamin binding
Specific function:
Vitamin B12-binding protein. Transports cobalamin into cells
Gene Name:
TCN1
Uniprot ID:
P20061
Molecular weight:
48206.3
General function:
Involved in cobalamin binding
Specific function:
Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum by specific receptor-mediated endocytosis
Gene Name:
GIF
Uniprot ID:
P27352
Molecular weight:
45415.7
General function:
Involved in calcium ion binding
Specific function:
Cotransporter which plays a role in lipoprotein, vitamin and iron metabolism, by facilitating their uptake. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the GIF-cobalamin complex. The binding of all ligands required calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. Interaction with LRP2 mediates its trafficking throughout vesicles and facilitates the uptake of specific ligands like GC, hemoglobin, ALB, TF and SCGB1A1. Interaction with AMN controls its trafficking to the plasma membrane and facilitates endocytosis of ligands. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface
Gene Name:
CUBN
Uniprot ID:
O60494
Molecular weight:
398672.8